Late Complications of Head and Neck Radiation
The most common adverse effect at clinically useful doses of pilocarpine is hyperhidrosis (excessive sweating); its incidence and severity are proportional to dosage. Also reported, typically at doses higher than 5 mg 3 times a day, are the following:
- Increased lacrimation.
- Bladder pressure (urinary urgency and frequency).
Pilocarpine usually increases salivary flow within 30 minutes after ingestion. Maximal response may occur only after continual use (>8 weeks).[Level of evidence: I]
It has been suggested that pilocarpine given during radiation therapy may reduce salivary gland impairment and xerostomia both during and after treatment. However, in a randomized study of 249 patients with HNC, the concomitant use of pilocarpine during radiation did not have a positive impact on quality of life or patient assessment of salivary function, despite the maintenance of salivary flow.[Level of evidence: I] It has been indicated that the efficacy of pilocarpine depends on the radiation dose distributed to the parotid glands during treatment, i.e., in patients in whom the mean parotid dose exceeds 40 Gy, pilocarpine may spare parotid gland function and reduce xerostomia—particularly significant after 12 months.[Level of evidence: I]
Cevimeline (30 mg 3 times a day) also appears anecdotally to have efficacy in managing radiation-induced xerostomia.;[Level of evidence: I] Although cevimeline is approved for use only in the management of Sjögren syndrome, appropriate clinical trials are under way, and its efficacy should be established soon. While cevimeline has greater selective affinity for M3 muscarinic receptors than pilocarpine, whether this can prove advantageous for treating radiation xerostomia remains unclear.
Acupuncture appears to offer an intervention for the treatment of radiation-induced xerostomia in patients with a residual functional capacity of the salivary glands and is a treatment modality without serious adverse effects.[21,22,23] Further randomized controlled clinical trials, including sham acupuncture, are warranted.
Intraoral electrical stimulation devices delivering a low-intensity electrical current to the oral mucosa—thus stimulating salivary gland secretion by innervating afferent neurons of the salivary reflex and efferent neurons (e.g., the lingual nerve)—is under development and has been tested, with promising initial results in the palliation of xerostomia.; Special considerations appear to be indicated when electrostimulation devices are used in head and neck radiation patients.[Level of evidence: I] Further studies are needed.